The alcohol-chronic disease relationship for some time has been a controversial topic in cardiovascular and alcohol epidemiology. Most research to date has focused on average alcohol volume and disregarded drinking patterns. Although a detrimental association of chronic heavy alcohol intake has been established for many chronic diseases, it has been shown that drinking patterns among moderate drinkers have an influence on disease risk, in particular ischemic heart disease (IHD) risk. This project will provide a necessary update of previous systematic reviews and meta-analyses on the relationship between average alcohol volume and cardiovascular diseases, type 2 diabetes, and gastro-intestinal diseases. Additionally, we will conduct novel systematic examinations of the influence of drinking patterns on these chronic diseases. For example, 14 drinks per week can be consumed on 2 heavy drinking occasions (i.e., 5 or more drinks on one occasion) on the weekend, or 2 drinks every day. The strong relationship of episodic heavy drinking found with IHD makes these investigations a timely undertaking. The proposed project will comprise of a comprehensive systematic literature review for the relationship of two dimensions of alcohol consumption, namely average alcohol volume and drinking pattern, with chronic diseases in order to systematically quantify the risk of death and disease among several distinct drinking groups. These drinking groups include lifetime abstainers, former drinkers, low to moderate non-heavy drinkers, low to moderate heavy drinkers (episodic heavy drinking), and chronic heavy drinkers. Specifically, we will test (H1) whether the risk relationship between lifetime abstainers and average alcohol volume is monotonically increasing (hemorrhagic stroke, hypertension, liver disease, and pancreatitis) or J-shaped (ischemic stroke and type 2 diabetes). Additionally, we will test (H2) whether former drinkers have an increased risk for chronic diseases compared to lifetime abstainers for all outcomes. Hypotheses 3 and 4 test the relationships between lifetime abstainers, low to moderate non-heavy drinkers, and episodic heavy drinkers. Hypotheses 5 and 6 test the association of acute alcohol intake on ambulatory systolic and diastolic blood pressure, alcoholic hepatitis, and acute pancreatitis. Results from primary studies will be pooled using fractional polynomials and categorical meta-analyses. All analyses will take into account the different effects alcohol drinking patterns can have for men and women because alcohol is metabolized differentially by sex. Other potential effect modifiers include race/ethnicity, age, smoking, body mass index, and co-morbidities, such as HIV or Hepatitis C status. There are currently no systematic investigations available for drinking patterns in relatio to chronic diseases examined in this project. Increasing rates of episodic heavy drinking patterns in the US, Canada, the UK, Denmark, and many other countries make this research project particularly timely. It will provide crucial evidence for estimates of harm from alcohol fo the Global Burden of Disease study, and the effect of different intervention policies for harm reduction on a population level.